The Agricultural Health Study (AHS) is a long-term prospective study of potential health effects associated with exposure to pesticides and other agricultural exposures. The study is a collaboration of the National Cancer Institute, the National Institute of Environmental Health Sciences, and the US Environmental Protection Agency. Farmers and their spouses and children are exposed to numerous potential hazards - many of which, such as pesticides, are relevant to the population at large. Farmers have been shown to be at increased risk for some cancers. Experimental and human studies of acute or high-dose exposures suggest that farmers may also be at increased risk of other adverse health effects. We are examining cancer incidence and other health endpoints in a prospective study of licensed pesticide applicators, spouses and children from North Carolina (NC) and Iowa (IA). Over a 3-year period, we enrolled more than 57,000 licensed applicators, representing 82% of eligible private pesticide applicators (largely farmers) in IA and NC and 43% of commercial applicators from Iowa. About 40% of the private applicators also completed a more detailed take-home questionnaire covering farming practices and health. Nearly 32,000 spouses of farmer applicators enrolled and 2/3 of these also provided data on reproductive health, including information on all children under age 21. Cancer incidence among the applicators, spouses, and children after five years of follow-up is currently being determined through linkage with the population-based cancer registries in IA and NC. Follow-up computer-assisted telephone interviews are used to update exposure information and to collect information on changes in health status since enrollment in the study. Buccal-cell samples are being collected from participants in order to extract DNA for future analyses of gene and environment interactions. In addition, a dietary assessment (food frequency questionnaire) is self-completed and returned by mail. In-depth assessment of agricultural exposures is being made for a small sample of farmers and their families in order to validate the questionnaires and facilitate exposure classification. Both environmental and biological samples are being collected. Interim analyses have characterized applicators and spouses and explored links between self-reported exposures and health status. For example, fungicide and organochlorine pesticide use was associated with increased risk for macular degeneration. Non-cancer outcomes of particular interest in this follow-up period include diabetes in children, Parkinson's Disease, autoimmune diseases, and premature ovarian failure. Preliminary results from the cancer linkage suggest that in-depth analyses of risk factors for prostate, lung and breast cancers will be feasible. A follow-up study of a subcohort of African American farmers and farmworkers includes health questionnaires, collection of a blood sample to measure DDE, lipids, and steroid hormones, and measures of adiposity and hair loss. Background: Farmers are exposed to many potential hazards that are also found in the general population. These include pesticides, solvents, metals, diesel exhaust, animals, grain dusts, and silica. Farmers appear to be at increased risk for several sepcific cancers and these cancers tend to be ones that are increasing in incidence throught the world. ALthough may studies have been done, much of this work has been retrospective or has been based on limited information on exposures. In addition, while there is some evidence for non-cancer health effects associated with many of these same exposures, much less work has been done. Finally, farmers are unique in that they live where they work. Thus their spouses and children are likely to be exposed both indrectly (e.g. through peesticide spray drif or tracking of chemicals and dusts into the home)or direectly as they also engage in farm chores including mixing and applying pesticides and dealing with other aspects of crop production.